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中国循证儿科杂志

中国循证儿科杂志 ›› 2022, Vol. 17 ›› Issue (1): 70-74.

• 论著 • 上一篇    下一篇

儿童伴IRF4基因重排大B细胞淋巴瘤6例病例系列报告并文献复习

张楠1,段彦龙1,周春菊2,金玲1,杨菁1,黄爽1,张梦1,张永红1   

  1.  国家儿童医学中心 首都医科大学附属北京儿童医院北京，100045；1 儿童肿瘤中心肿瘤内科，北京市儿童血液肿瘤重点实验室，儿科重大疾病研究教育部重点实验室，2 病理科 
  • 收稿日期:2021-12-09 修回日期:2022-01-24 出版日期:2022-02-25 发布日期:2022-02-25
  • 通讯作者: 段彦龙

6 cases of large B-cell lymphoma with IRF4 gene rearrangement in children：A case series report and literature review

ZHANG Nan1， DUAN Yanlong1， ZHOU Chunju2， JIN Ling1， YANG Jing1， HUANG Shuang1，ZHANG  Meng1，ZHANG Yonghong1   

  1. National Center for Children's Health ,Beijing Children's Hospital ,Capital Medical University, Beijing  100045,China; 1 Medical Oncology Department, Pediatric Oncology Center, Key Laboratory of Pediatric Hematology Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education; 2 Department of Pathology
  • Received:2021-12-09 Revised:2022-01-24 Online:2022-02-25 Published:2022-02-25
  • Contact: DUAN Yanlong, email: duanyanlong@hotmail.com

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摘要： 背景：儿童伴干扰素调节因子4（IRF4）基因重排大B细胞淋巴瘤（LBCL）在WTO淋巴瘤分类（2017）中被定义为一种独特亚型，临床罕见,有其特殊的临床特征，有必要将其与其他LBCL进行区分。 目的：探讨儿童伴IRF4基因重排LBCL的临床表现、病理特点、治疗方案和预后等方面的特征。 设计：病例系列报告。 方法：回顾性收集2018年5月至2021年10月首都医科大学附属北京儿童医院（我院）诊治的伴IRF4基因重排LBCL患儿的临床资料，总结临床特征，检索PubMed、万方和知网数据库，行文献复习。 主要结局指标：伴IRF4基因重排的LBCL患儿的完全缓解率。 结果：本文纳入6例，占同期我院收治侵袭性成熟B细胞淋巴瘤的2.7%，男5例，女1例；发病年龄7（4~13）岁。瘤灶受累部位局限于头颈部4例、肠道1例，头颈部及肠道1例。起病至随访期间均未发现转移。临床分期Ⅱ期4例，Ⅲ期2例。文献检索到56例，合并本文共62例伴IRF4基因重排的LBCL患儿，男38例（61.2%），起病年龄为11.2（3，18）岁，瘤灶主要受累部位为头颈部（79%）、肠道及腹股沟（21%）；多为孤立病灶，起病至随访期间均未发现转移。临床分期Ⅰ~Ⅱ期占79%。本文6例光镜下2例呈现完全结节状滤泡样结构、表现为大小不一的结节，缺乏套区及吞噬核碎片形成的“星空现象”；4例呈现完全弥漫样结构，表现为肿瘤细胞中等大小或偏大，核染色质分散，可见小的嗜碱性核仁。免疫组化均表达CD20、PAX5和BCL6，MUM1强表达，Ki67阳性指数90%~95%，3例CD10、BCL2阳性，6例荧光原位杂交（FISH）检测到IRF4重排，均未检测到BCL6、BCL2及CMYC基因重排。62例显示完全弥漫样结构占43.5%，完全结节状滤泡样结构37.1%，混合样19.4%；88.7%可检测出伴IRF4的重排。 结论：伴IRF4重排的LBCL临床罕见，肿瘤受累部位以头颈部为主，临床分期以早期病变为主，多为孤立及惰性，进展慢，侵袭性弱，预后好；病理形态表现为完全弥漫样、滤泡样及混合样结构，免疫组化均表达CD20、PAX5和BCL6，MUM1强表达，Ki67阳性指数较高，FISH结合二代基因测序可检测出IRF4重排。

关键词: 伴IRF4基因重排的大B细胞淋巴瘤, 儿童, 治疗, 预后

Abstract: Background: Large Bcell lymphoma in children with interferon regulatory factor 4(IRF4)gene rearrangement is defined as a unique subtype in the 2017 WTO lymphoma classification. Since it is clinically rare with special clinical features, it is necessary to distinguish it from other large Bcell lymphomas. Objective: To investigate the clinical manifestations, pathological features, treatment and prognosis of large Bcell lymphoma with IRF4 gene rearrangement in children. Design: Case series report. Methods: The clinical data of children with large Bcell lymphoma with IRF4 gene rearrangement diagnosed and treated in Beijing Children's Hospital affiliated to Capital Medical University from May 2018 to October 2021 were collected retrospectively. The clinical characteristics were summarized, and PubMed, Wanfang and CNKI were searched for literature review. Main outcome measures: Complete response rate of large Bcell lymphoma in children with IRF4 gene rearrangement. Results: Six cases were included in the analysis, accounting for 2.7% of the invasive mature Bcell lymphoma treated in our hospital in the same period. There were 5 males (83.3%) and 1 female. The age of onset was 7 (4 13) years old. The involved sites were the neck and head in 4 cases, the intestine in 1 case and both of the head and neck and intestine in 1 case. No metastasis was found from the onset to followup. Four cases were in stageⅡ and 2 cases were in stage Ⅲ. Among the 62 cases including 56 from literature review, 61.2% were male, the age of onset was 11.15 (3,18) years old, the main site of tumor was 79% in the head and neck, and 21% in the intestine and groin. Most of them were isolated lesions, and no metastasis was found from the onset to followup. Clinical stage ⅠⅡ accounted for 79%. Under light microscope, 2 of 6 cases showed complete nodular follicular structure featured by nodules of different sizes, lack of "starry sky phenomenon" formed by mantle area and phagocytic nuclear fragments and 4 cases showed completely diffuse like structure with medium or large tumor cells, scattered nuclear chromatin and small basophilic nucleoli. Immunohistochemistry showed the expression of CD20 and PAX5, the strong expression of BCL6 and MUM1, and the positive index of 90% to 95% for Ki67. Three cases were positive for CD10 and BCL2, six cases were positive for IRF4 rearrangement by fluorescence in situ hybridization (FISH), and BCL6, BCL2 and CMYC gene rearrangements were not detected. Sixtytwo cases showed complete diffuse like structure (43.5%), complete nodular follicular like structure (37.1%) and mixed like structure (19.4%) and 88.7% could detect rearrangement with IRF4 . Conclusion: Large Bcell lymphoma with with IRF4 rearrangement is clinically rare. The tumor is mainly involved in the head and neck. The clinical stage is mainly early lesions, which are more isolated and inert, slow progress, weak invasiveness and good prognosis. The pathological morphology showed complete diffuse like, follicular like and mixed like structures. Immunohistochemistry showed the expression of CD20 and PAX5, the strong expression of BCL6 and MUM1, and the high positive index of Ki67. IRF4 rearrangement could be detected by FISH combined with secondgeneration gene sequencing.

Key words: large B-cell lymphoma with IRF4 gene rearrangement, children, treatment, prognosis